We request funds to purchase a Zeiss LSM 510 NLO confocal microscope, augmented by a Coherent MiraX-ZFC laser system for multi- photon microscopy. Seven Major Users and eleven other users, well funded by NIH (26 separate research grants), describe twenty research projects that span a broad range of biological questions and will collectively utilize all of the capabilities of the instrument. The applicants represent seven different departments in the School of Medicine. The Dean has made a commitment of $200,000 for support of the facility, and other faculty have made additional commitments of funds, equipment, and space. Dr. Winfried Denk (Bell Labs) will serve as External Advisor. He and Dr. Graham Ellis-Davies (Philadelphia) will collaborate with Major Users on two research projects. A new graduate 6ourse, "Optical Measurement of Cellular Function in Live Cells" will be offered as part of an expanding optical microscopy facility. Major Users have had extensive experience with various imaging techniques, and have acquired sound preliminary data that illustrate both the need for this equipment and the feasibility of the proposed experiments. A comprehensive inventory of existing equipment and careful scrutiny of proposals make clear that none of the projects can be accomplished with current equipment at the Health Science Center or any other campus in reasonable proximity. A stable and time-tested management plan that has emerged over the past ten years of continuous administration of shared optical facilities by the same personnel will insure that the instrument will be well maintained, that it will become self-supporting, and that it will be used intensively by well- trained scientists drawn both from the User Group and, over time, from the larger population of scientists in the region.